Regulation of translation
- Created by: natasha8sherry
- Created on: 12-01-14 12:54
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- Regulation of translation
- can be global or mRNA specific
- mRNA specific
- means of controlling gene expression in cells where transcription is repressed or absent
- means of producing the right amount of the right proteins at the right time
- global
- eIF4E-bp
- stimulated by environmental factors, such as stress, viral infection, starvation and heat shock
- eIF2 is phosphorylated at its alpha subunit during viral infection
- results in generalised global translational repression
- global upredulation does occur
- phosphorylation of the eIF4E-binding protein
- normally sequesters eIF4E but here causes it to be released so it can interact with eIF4G and form the translation machinery
- phosphorylation of the eIF4E-binding protein
- eIF4E-bp
- mRNA specific
- The ferritin gene
- regulation by RNA-binding proteins as opposed to translation initiation factors
- control of iron levels in cells
- normally tightly regulated as iron plays role in active site of many enzymes
- excess iron can oxidise cellular compartments
- when iron level high therefore necessary to prevent toxic levels accumulating
- iron levels low - available free iron needs to be released in order for iro-dependent enzymes to operate
- ferritin sequesters iron in cells
- 5'UTR of ferritin mRNA contains iron response elements - hairpin stem-loop structures
- act as binding sites for the iron response-building proteins
- IRP1
- IRP2
- in absence of iron IRP1 and IRP2 bind the iron response elements very well, preventinf the small ribosomal subunit from scanning the ferritin mRNA for the AUG start codon
- in presence of iron, IRP1 and IRP2 are rendered inactive and cannot bind the response element, so ferritin mRNA can be translated
- ferritin protein produced which sequesters iron and prevents toxic levels
- act as binding sites for the iron response-building proteins
- 5'UTR of ferritin mRNA contains iron response elements - hairpin stem-loop structures
- transferrin receptor
- binds to the transferring protein that carries iron around the blood
- encoded by the TfR gene
- able to import transferrin that is complexed to iron into a cell
- iron response elements also present (at the 3'UTR of the TfR mRNA this time
- presence of iron
- iron response elements not occupied by IRPs
- TfR mRNA unstable and degraded
- less protein made - therefore less iron transported into cells
- TfR mRNA unstable and degraded
- iron response elements not occupied by IRPs
- absence of iron
- IRPs bound to iron response elements on TfR mRNA
- TfR mRNA protected from degradation and stable
- more TfR protein made - more iron transported into cells to be used in active site of enzymes
- TfR mRNA protected from degradation and stable
- IRPs bound to iron response elements on TfR mRNA
- presence of iron
- regulation by miRNAs
- non-coding RNAs
- regulate target genes at the level of translation
- lin-4 miRNA
- in C.elegans
- binds to 3'UTR of lin-14 and lin-28 mRNAs
- genes expressed in developmental timing
- results in translational repression - normal event in normal development
- developmental coregulation proteins
- A-P system in Drosophila is established by BICOID morphogen gradient
- bicoid protein is organiser of anterior development
- gradient involves several morphogens e.g. hunchback, caudal and nanos
- bicoid mRNA translated mainly at the anterior end of an oocyte
- then inhibits translation of caudal mRNA at the anterior end
- at posterior end, nanos protein inhibits translation of hunchback mRNA
- no hunchback protein at the posterior end
- A-P system in Drosophila is established by BICOID morphogen gradient
- can be global or mRNA specific
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